The activity of calcium-activated neutral proteases (CANP) and acid proteases has been studied in the squid nervous system as well as the rat erythrocyte ghost. In the squid, nerve cell bodies and axons contain abundant CANP activity, whereas nerve terminals (i.e., optic lobe synaptosomes) do not. In contrast, the axon contains no detectable acid (lysosomal) protease whereas the cell bodies and nerve terminals contain significant levels of these acid hydrolases. Ethanol appeared to increase acid protease activity in the squid nerve terminals (synaptosomes). CANP acitivty was also studied in erythrocyte ghosts isolated from normal and alcohol treated rats. Ghosts prepared from alcohol dependent-intoxicated animals contained more than twice as much CANP activity as control erythrocyte ghosts. Ghosts from acute-intoxicated, and withdrawing animals were about 50% greater in CANP activity. These studies provide information on the role of calcium-activated proteases in nervous tissue and erythrocyte ghosts, and on the effects of alcohol on these proteases. The studies also suggest that alcohol may alter erythrocyte and nervous system proteins by increasing the activity of calcium activated and acid proteases.